title: Photouncaging nanoparticles for MRI and fluorescence imaging in vitro and in vivo.
abstract: Multimodal and multifunctional nanomaterials are promising candidates for bioimaging and therapeutic applications in the nanomedicine settings. Here we report the preparation of photouncaging nanoparticles with fluorescence and magnetic modalities and evaluation of their potentials for in vitro and in vivo bioimaging. Photoactivation of such bimodal nanoparticles prepared using photouncaging ligands, CdSe/ZnS quantum dots, and super paramagnetic iron oxide nanoparticles results in the systematic uncaging of the particles, which is correlated with continuous changes in the absorption, mass and NMR spectra of the ligands. Fluorescence and magnetic components of the bimodal nanoparticles are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and elemental analyses using energy dispersive X-ray (EDX) spectroscopy and X-ray photoelectron spectroscopy (XPS). Bioconjugation of the nanoparticles with peptide hormones renders them with biocompatibility and efficient intracellular transport as seen in the fluorescence and MRI images of mouse melanoma cells (B16) or human lung epithelial adenocarcinoma cells (H1650). Biocompatibility of the nanoparticles is evaluated using MTT cytotoxicity assays, which show cell viability over 90%. Further, we combine MRI and NIR fluorescence imaging in C57BL/6 (B6) mice subcutaneously or intravenously injected with the photouncaging nanoparticles and follow the in vivo fate of the nanoparticles. Interestingly, the intravenously injected nanoparticles initially accumulate in the liver within 30 min post injection and subsequently clear by the renal excretion within 48 h as seen in the time-dependent MRI and fluorescence images of the liver, urinary bladder, and urine samples. Photouncaging ligands such as the ones reported in this article are promising candidates for not only the site-specific delivery of nanomaterials-based contrast agents and drugs but also the systematic uncaging and renal clearance of nanomaterials after the desired in vivo application.
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Edakkattuparambil S
authors.initials: ES
authors.lastname: Shibu
authors.forename: Kenji
authors.initials: K
authors.lastname: Ono
authors.forename: Sakiko
authors.initials: S
authors.lastname: Sugino
authors.forename: Ayami
authors.initials: A
authors.lastname: Nishioka
authors.forename: Akikazu
authors.initials: A
authors.lastname: Yasuda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shigeri
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Wakida
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Vasudevanpillai
authors.initials: V
authors.lastname: Biju
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008027:Light; D008099:Liver / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D045663:Quantum Dots; D013052:Spectrometry, X-Ray Emission
chemical_list: D001672:Biocompatible Materials; D005290:Ferric Compounds; D008024:Ligands; D010455:Peptides; C000499:ferric oxide